Bioequivalence Phase I Study of BFI-751 Compared With EU and US-STELARA® in Healthy Adults

NCT04843631 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BFTA-AU-001
• Study Type: interventional
• Target: 216
• Locations: 2 countries
• Sites: 3

Brief Summary

BFI-751 is being developed by BioFactura Australia Pty Ltd as a biosimilar drug to Stelara® (EU licenced and US licenced) (ustekinumab) is a prescription biologic medicine used to treat people with Crohn's disease, Ulcerative Colitis, plaque psoriasis and psoriatic arthritis. Stelara® is an immune suppressant that reduces the effects of inflammatory proteins within the body. This is the first time BFI-751 will be given to humans. The primary purpose of this study is to compare the pharmacokinetics (the study of what the body does to the drug, referring to the movement of any drug going into, through, and out of the body) by checking to see if the blood levels of 751-BFI are comparable with US-Stelara® and EU-Stelara® following a single injection under the skin. The secondary purposes of this study are:

• to assess the safety of BFI-751,
• study how well the healthy volunteers tolerate it and
• to also assess the immune response to it in healthy volunteers.

Conditions

Psoriasis

Outcome Measures

Primary Outcomes (8)

• Bioequivalence- Cmax

  Compare Maximum observed concentration (Cmax) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

• Bioequivalence-Tmax

  Compare Time to Cmax (Tmax) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

• Bioequivalence - Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-tlast)

  Compare Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-tlast) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

• Bioequivalence - Total AUC after extrapolation from time t to time infinity (AUC0-inf)

  Compare Total AUC after extrapolation from time t to time infinity (AUC0-inf) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

• BioEquivalence - Elimination rate constant (Kel)

  Compare Elimination rate constant (Kel) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

• Bioequivalence - Apparent terminal elimination half-life (t1/2)

  Compare Apparent terminal elimination half-life (t1/2) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

• Bioequivalence - Volume of distribution (Vz)

  Compare Volume of distribution (Vz) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

• Bioequivalence - Apparent clearance (CL)

  Compare Apparent clearance (CL) of BFI-751 with EU-Stelara and US-Stelara following a single 45 mg SC injection

  From Baseline to Day 85

Secondary Outcomes (31)

• Safety and tolerability - Incidence, type and severity of Adverse Events

  From Baseline to Day 85

• Safety and tolerability - Changes from baseline in clinical laboratory results (haematology, serum chemistry, coagulation, and urinalysis)

  From Baseline to Day 85

• Changes from baseline in vital signs parameter - systolic and diastolic blood pressure in mmHg

  From Baseline to Day 85

• Changes from baseline in vital signs parameter - heart rate in beats per minute

  From Baseline to Day 85

• Changes from baseline in vital signs parameter - respiratory rate in breaths per minute

  From Baseline to Day 85

Study Arms (3)

Arm A: BFI-751

EXPERIMENTAL

On Day 1, participants will be randomised to receive a single SC dose of 45 mg/0.5mL BFI-751

Drug: BFI-751

Arm B: EU-STELARA®

ACTIVE COMPARATOR

On Day 1, participants will be randomised to receive a single SC dose of 45 mg/0.5mL EU- STELARA®

Drug: EU-STELARA®

Arm C: US-STELARA®.

ACTIVE COMPARATOR

On Day 1, participants will be randomised to receive a single SC dose of 45 mg/0.5mL US- STELARA®

Drug: US-STELARA®

Interventions

BFI-751 DRUG

Single use vial, solution

Also known as: Ustekinumab Biosimilar

Arm A: BFI-751

EU-STELARA® DRUG

Pre-filled syringe, solution

Also known as: STELARA® (ustekinumab)

Arm B: EU-STELARA®

US-STELARA® DRUG

Pre-filled syringe, solution

Also known as: STELARA® (ustekinumab)

Arm C: US-STELARA®.

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers will be included in the study if they meet all of the following criteria at screening, and after check-in on Day -1, prior to dose administration:
• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Adult male and female volunteers, 18 to 50 years of age (inclusive).
• Subjects who smoke no more than 2 cigarettes or equivalent per week can be included in the study but must be willing to abstain from smoking 7 days prior to admission and during the confinement period. Subjects must have a negative test for cotinine prior to check-in on Day -1.
• Body mass index (calculated) within the range of 18 to 32 kg/m2 inclusive.
• Body weight ≥ 50 kg and ≤ 100 kg inclusive.
• Medically healthy without clinically significant abnormalities, including:
• Physical examination without any clinically significant findings, in the opinion of the Investigator.
• Systolic blood pressure (BP) in the range of 90 to 145 mm Hg (inclusive) and diastolic BP in the range of 50 to 90 mm Hg (inclusive) after at least 5 minutes in the supine position.
• Heart rate (HR) in the range of 40 to 100 beats/min (inclusive) after at least 5 minutes rest in a supine position.
• Normal body temperature 35.5 to 37.7°C (inclusive).
• Triplicate 12-lead electrocardiogram (ECG), taken after the volunteer has been supine for at least 5 minutes, with a QT interval corrected using the Fridericia method (QTcF) ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities, in the opinion of the Investigator.
• No clinically significant findings in serum chemistry, haematology, coagulation and urinalysis examinations, in the opinion of the Investigator.
• Assessments may be repeated once, if abnormal values were recorded in the first instance, at the discretion of the Investigator.
• Female volunteers must:

You may not qualify if:

• Healthy volunteers will be excluded from the study if there is evidence of any of the following at screening or after check-in on Day -1, prior to dose administration:
• \. Prior exposure to STELARA® (Ustekinumab).
• Have a history of hypersensitivity or allergic reactions (either spontaneous or following drug administration) to any of the active or formulation ingredients of the study treatments components.
• Have a history of or presence of disease determined by the PI to be clinically significant including:
• gastrointestinal (including diverticulitis, stomach ulcers, inflammatory intestinal disease, gastrointestinal perforations/fistulae/intra-abdominal abscess).
• any other internal, non-gastrointestinal fistulae that is at an increased risk of bleeding.
• haematological (including pancytopenia, aplastic anaemia or blood dyscrasia).
• renal, hepatic, pulmonary, neurologic, psychiatric, metabolic (including known diabetes mellitus), or
• allergic disease excluding mild asymptomatic seasonal allergies.
• Have a history of prolonged immunosuppressant therapy, or photochemotherapy treatment.
• Presence or evidence of recent sunburn, scar tissue, tattoo (more than 25% of body area), open sore or branding that, in the opinion of the Investigator, would interfere with interpretation of skin adverse reactions.
• Have a history of and/or current cardiac disease defined as one of the following:
• History of congestive heart failure; angina pectoris requiring anti-anginal medication.
• Evidence of transmural infarction on ECG.
• History of sustained hypertension (systolic \> 180 mmHg and/or diastolic \> 100 mmHg) or hypertensive crisis or hypertension encephalopathy.

Sponsors & Collaborators

• BioFactura Australia Pty Ltd.: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (3)

Nucleus Network

Brisbane, Queensland, 4029, Australia

Location

CMAX

Adelaide, South Australia, 5000, Australia

Location

NZCR

Grafton, Auckland, 1010, New Zealand

Location

Related Publications (1)

• Hausfeld JN, Challand R, McLendon K, Macapagal N, Bruce-Staskal P, Fiaschetti C, Sampey DB. Pharmacokinetic Profiles of a Proposed Biosimilar Ustekinumab (BFI-751): Results From a Randomized Phase 1 Trial. Clin Pharmacol Drug Dev. 2023 Oct;12(10):1001-1012. doi: 10.1002/cpdd.1305. Epub 2023 Jul 22.

  PMID: 37483071 DERIVED

MeSH Terms

Conditions

Psoriasis

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jeffrey N Hausfeld, MD

  BioFactura Australia Pty Ltd.

  STUDY DIRECTOR

• Kristi McLendon

  Nucleus Network

  PRINCIPAL INVESTIGATOR

• Emir Redzepagic

  CMAX

  PRINCIPAL INVESTIGATOR

• Christian Schwabe

  NZCR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is double-blinded. Sealed participant-specific code break envelopes will be produced by the unblinded statistician so that the treatment assigned to each participant can be obtained if required, in an emergency only, where knowledge of the randomisation code is required to provide appropriate treatment. The code break envelopes will be retained at the clinical unit in a secure, accessible location. Those blinded to study drug assignment include the sponsor, the PI, clinical study personnel participating in participants' care or clinical evaluations, and the study participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double blinded, randomized, parallel group

Study Record Dates

• First Submitted: March 23, 2021
• First Posted: April 13, 2021
• Study Start: April 1, 2021
• Primary Completion: December 8, 2021
• Study Completion: December 8, 2021
• Last Updated: March 25, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); NZ (1)